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Vinflunine

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https://www.readbyqxmd.com/read/29606979/pd-1-and-pd-l1-inhibitors-after-platinum-based-chemotherapy-or-in-first-line-therapy-in-cisplatin-ineligible-patients-dramatic-improvement-of-prognosis-and-overall-survival-after-decades-of-hopelessness-in-patients-with-metastatic-urothelial-cancer
#1
REVIEW
Irene Resch, Shahrokh F Shariat, Kilian M Gust
Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control...
2018: Memo
https://www.readbyqxmd.com/read/29590008/health-related-quality-of-life-analysis-from-keynote-045-a-phase-iii-study-of-pembrolizumab-versus-chemotherapy-for-previously-treated-advanced-urothelial-cancer
#2
David J Vaughn, Joaquim Bellmunt, Yves Fradet, Jae Lyun Lee, Lawrence Fong, Nicholas J Vogelzang, Miguel A Climent, Daniel P Petrylak, Toni K Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stephane Culine, Cora N Sternberg, Yabing Mai, Haojie Li, Rodolfo F Perini, Dean F Bajorin, Ronald de Wit
Purpose In the phase III KEYNOTE-045 study ( ClinicalTrials.gov identifier: NCT02256436), pembrolizumab significantly prolonged overall survival compared with investigator's choice of chemotherapy in patients with previously treated advanced urothelial cancer. Here, we report the results of health-related quality-of-life (HRQoL) analyses from the KEYNOTE-045 trial. Patients and Methods Patients were randomly assigned 1:1 to pembrolizumab 200 mg or investigator's choice of docetaxel 75 mg/m2 , paclitaxel 175 mg/m2 , or vinflunine 320 mg/m2 administered intravenously every 3 weeks...
March 28, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29492236/monoinstitutional-real-world-experience-in-management-of-vinflunine-as-second-line-therapy-for-transitional-cell-carcinoma-of-the-urothelium
#3
Giovanni Schinzari, Ernesto Rossi, Francesco Pierconti, Giovanna Garufi, Santa Monterisi, Antonia Strippoli, Ettore D'Argento, Alessandra Cassano, Carlo Barone
Vinflunine is the only cytotoxic agent tested as a second line therapy in transitional cell carcinoma of the urothelium in a phase III trial. It is not largely employed in clinical practice because of the high incidence of grade 3-4 toxicity. We evaluated efficacy and safety of Vinflunine at the dose of 280 mg/m2 every 3 weeks associated with primary prophylaxis with granulocyte growth factors and laxatives for patients progressed after platinum + Gemcitabine. Overall survival was 8.5 months, progression-free survival 4...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29481630/open-label-randomised-phase-iii-trial-of-vinflunine-versus-an-alkylating-agent-in-patients-with-heavily-pretreated-metastatic-breast-cancer
#4
J Cortes, J Perez-Garcia, C Levy, P Gómez Pardo, H Bourgeois, S Spazzapan, N Martínez-Jañez, T-C Chao, M Espié, J M Nabholtz, X Gonzàlez Farré, V Beliakouski, J Román García, E Holgado, M Campone
Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy...
February 21, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29454321/safety-and-efficacy-of-temsirolimus-as-second-line-treatment-for-patients-with-recurrent-bladder-cancer
#5
Marina Pulido, Guilhem Roubaud, Anne-Laure Cazeau, Hakim Mahammedi, Lionel Vedrine, Florence Joly, Loic Mourey, Christian Pfister, Alejandro Goberna, Barbara Lortal, Carine Bellera, Philippe Pourquier, Nadine Houédé
BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29447329/randomised-phase-iii-trial-of-vinflunine-plus-capecitabine-versus-capecitabine-alone-in-patients-with-advanced-breast-cancer-previously-treated-with-an-anthracycline-and-resistant-to-taxane
#6
M Martin, M Campone, I Bondarenko, D Sakaeva, S Krishnamurthy, L Roman, L Lebedeva, J-C Vedovato, M Aapro
Background: Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting, and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods: Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine (825 mg/m2 twice daily [bid], days 1-14) every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 bid, days 1-14) q3w...
February 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29416444/vinflunine-for-the-treatment-of-advanced-or-metastatic-transitional-cell-carcinoma-of-the-urothelial-tract-an-evidence-based-review-of-safety-efficacy-and-place-in-therapy
#7
REVIEW
Steven C Brousell, Joseph J Fantony, Megan G Van Noord, Michael R Harrison, Brant A Inman
Background: A systematic review and meta-analysis of the use of systemic vinflunine (VIN) in the treatment of urothelial carcinoma (UC) was performed to evaluate its efficacy based on current available clinical data. Methods: This review was prospectively registered at the International Prospective Register of Systematic Reviews, PROSPERO (registration CRD42016049294). Electronic databases including MEDLINE®, Embase®, Cochrane Central Register of Controlled Trials, and Web of Science were searched through December 2016...
2018: Core Evidence
https://www.readbyqxmd.com/read/29402855/vinflunine-in-advanced-transitional-cell-cancer-of-the-urothelial-tract-a-potential-option-for-maintenance-therapy-a-case-series
#8
Raffaella Palumbo, Luca Licata, Federico Sottotetti, Barbara Tagliaferri, Emma Pozzi, Cristina Teragni, Erica Quaquarini, Antonio Bernardo
INTRODUCTION: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy. METHODS: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29341179/better-characterization-of-vinflunine-pharmacokinetics-variability-and-exposure-toxicity-relationship-to-improve-its-use-analyses-from-18-trials
#9
A Schmitt, L Nguyen, G Zorza, P Ferré, A Pétain
AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29239187/-immunotherapy-for-bladder-cancer
#10
T Büchler
Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29219016/pembrolizumab-in-the-treatment-of-advanced-urothelial-cancer
#11
Kevin T Lundgren, Matthew S Farina, Joaquim Bellmunt
Pembrolizumab is a humanized monoclonal antibody that targets PD-1. In the Phase III trial KEYNOTE-045, pembrolizumab was associated with a significant overall survival benefit when compared with docetaxel, paclitaxel and vinflunine in second line metastatic urothelial carcinoma (UC). Additionally, in the first line, early results from an interim analysis of the Phase II trial Keynote-052 study indicated that pembrolizumab is efficacious for cisplatin-ineligible patients. Based on data from these trials, pembrolizumab was the most recent among the five checkpoint inhibitors tested in UC to be approved by the US FDA in May 2017...
December 2017: Future Oncology
https://www.readbyqxmd.com/read/29081023/combined-treatment-with-pemetrexed-and-vinflunine-in-patients-with-metastatic-urothelial-cell-carcinoma-after-prior-platinum-containing-chemotherapy-results-of-an-exploratory-phase-i-study
#12
H Pappot, H von der Maase, A Ullén, M Agerbæk
Vinflunine is to date the only registered agent for second-line treatment of metastatic urothelial cell carcinoma (UCC) in Europe. However, the effect is modest. Pemetrexed has demonstrated some single-agent activity in this disease entity. In order to improve treatment possibilities for UCC patients, a phase I trial (VINTREX) was undertaken to assess the safety of vinflunine and pemetrexed in metastatic UCC patients. A dose escalation design was planned to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a vinflunine/pemetrexed combination...
October 28, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29061830/vinflunine-in-the-treatment-of-upper-tract-urothelial-carcinoma-subgroup-analysis-of-an-observational-study
#13
COMPARATIVE STUDY
Hendrik Heers, Patrick DE Geeter, Peter J Goebell, Ullrich Matz, Wito DE Schultz, Birgit Edlich, Margitta Retz, Axel Hegele
BACKGROUND/AIM: Despite an expected prognostic disadvantage for upper tract versus lower tract metastatic urothelial carcinomas (UTUC/LTUC), only few studies have been conducted to elucidate potential differences in chemotherapy treatment. PATIENTS AND METHODS: A post-hoc subgroup analysis of a non-interventional study investigating vinflunine after failure of a platinum-based chemotherapy in metastatic/locally advanced UC patients was performed. RESULTS: A total of 18 and 59 out of 77 patients had UTUC and LTUC, respectively...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29040706/inhibition-of-survivin-expression-after-using-oxaliplatin-and-vinflunine-to-induce-cytogenetic-damage-in-vitro-in-lymphocytes-from-colon-cancer-patients-and-healthy-individuals
#14
Amal A A Alotaibi, Mojgan Najafzadeh, Justin D Davies, Adolf Baumgartner, Diana Anderson
Chemotherapy drugs usually inflict a lethal dose to tumour cells with the consequence that these cells are being killed by cell death. However, each round of chemotherapy also causes damage to normal somatic cells. The DNA cross-linking agent oxaliplatin (OXP), which causes DNA double-strand breaks, and vinflunine (VFN), which disrupts the mitotic spindle, are two of these chemotherapy drugs which were evaluated in vitro using peripheral lymphocytes from colorectal cancer patients and healthy individuals to determine any differential response...
October 17, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29035832/new-insights-into-vinca-alkaloids-resistance-mechanism-and-circumvention-in-lung-cancer
#15
REVIEW
Ying Zhang, Shao-Hui Yang, Xiu-Li Guo
Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28724419/real-life-clinical-practice-results-with-vinflunine-in-patients-with-relapsed-platinum-treated-metastatic-urothelial-carcinoma-an-italian-multicenter-study-movie-goirc-01-2014
#16
Rodolfo Passalacqua, Silvia Lazzarelli, Maddalena Donini, Rodolfo Montironi, Rosa Tambaro, Ugo De Giorgi, Sandro Pignata, Raffaella Palumbo, Giovanni Luca Ceresoli, Gianluca Del Conte, Giuseppe Tonini, Franco Morelli, Franco Nolè, Stefano Panni, Ermanno Rondini, Annalisa Guida, Paolo Andrea Zucali, Laura Doni, Elisa Iezzi, Caterina Caminiti
BACKGROUND: Vinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice...
July 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28633191/-urothelial-cancer-update-on-systemic-treatment-options
#17
Günter Niegisch
Perioperative chemotherapy is likely to improve survival in both the neoadjuvant and the adjuvant setting. Therefore, it is an integral part of the modern treatment of patients with muscle-invasive urothelial bladder cancer. All patients who are suitable for cisplatin-based chemotherapy should be involved in a corresponding concept.Cisplatin-based combinations are standard regimens in the perioperative and palliative systemic treatment of urothelial cancer. Carboplatin is only an inferior substitute for "unfit" patients in the palliative treatment situation...
August 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28591872/-the-role-of-immunooncology-in-the-treatment-of-urothelial-cancer
#18
Margitta Retz, Robert Tauber, Thomas Horn
Data published in November 2016 showed a significant survival benefit for the PD-1 antibody Pembrolizumab in the second-line treatment of metastatic urothelial cancer in comparison to standard chemotherapy. Other PD-1/PD-L1 antibodies are being tested in advanced clinical trials. This class of substances will become standard of care from the time of their approval which is expected for 2017 and will replace vinflunine, which is currently recommended in the German guideline. PD-1/PD-L1 directed substances are also being tested as a first line treatment of metastatic urothelial carcinoma...
August 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28588741/erratum-vinflunine-treatment-in-patients-with-metastatic-urothelial-cancer-a-nordic-retrospective-multicenter-analysis
#19
Karin Holmsten, Line Dohn, Niels Viggo Jensen, Carl-Henrik Shah, Fredrik Jäderling, Helle Pappot, Anders Ullén
[This corrects the article DOI: 10.3892/ol.2016.4775.].
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28466878/urological-cancer-vinflunine-is-an-effective-maintenance-therapy
#20
Peter Sidaway
No abstract text is available yet for this article.
June 2017: Nature Reviews. Clinical Oncology
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